Formation, Regulation, and Eradication of Bacterial Biofilm in Human Infection

*Muhammad Usman, Huan Yang, Jun-Jiao Wang, Jia-Wei Tang, Li-Yan Zhang and Liang Wang*

#### **Abstract**

Microbial biofilms are complicated structures in which planktonic cells change to a sessile form of growth. The development of an extracellular polymeric substance (EPS) matrix, which encloses the bacterial cells and offers additional protection, supports that kind of growth. Biofilms present a significant threat to public health due to their extreme resistance to higher antibiotic concentrations. In addition, biofilms are also resistant to human immune systems. Bacterial biofilms can spread their pathogenicity through a variety of approaches, such as adhering to a solid surface, evading host defenses like phagocytosis, generating a large amount of toxins, resisting anti-microbial agents, transferring genes to generate more virulent strains, and dispersing microbial aggregates that transport the microorganisms to new locations. Consequently, there is an urgent need to replace the widespread procedure of antibiotics with novel developing approaches. Furthermore, biofilm formation has been connected with high rates of disease, health-related infections, and even death, leading to the search for alternative treatment approaches. The review intends to provide information about clinically important bacterial pathogens of the gut, mouth, skin, and lungs and insights into the different perceptions of microbial biofilms, as well as their formation, regulation, and pathogenicity. In addition, for efficient eradication or inhibition of biofilms and associated infections, nanoparticle approaches for addressing persistent bacterial infections have also been discussed.

**Keywords:** biofilm, bacterial infection, pathogenicity, antibiotic resistance, nanoparticles

### **1. Introduction**

The term "biofilm" refers to a connection of microorganisms when microbial cells adhere to one another on living or inactive surfaces and are enclosed in an extracellular polymeric substance (EPS) matrix [1]. The initial identification of microbial biofilm belongs to a Dutch researcher Antoni van Leeuwenhoek, who used a simple microscope to detect "animalcules" for the first time on the surfaces of teeth [2]. A number of studies have demonstrated that bacterial biofilms are resistant to

antibiotics and cannot be hindered by human immune system because the microbes that cause biofilms have a greater capacity to resist or remove antimicrobial agents, which extends the period of recovery during infection [3]. During biofilm-forming stage, certain genes of bacteria are induced, resulting in the activation of stressrelated genes and the transformation of bacteria into resistant phenotypes which lead to changes in cell density, pH, osmolarity, or nutrition [4]. It has been reported that majority of bacteria have the ability to develop biofilm on almost every type of surface, which poses a significant threat to the health of people because of the diseases it causes and the resistance it provides to many antibiotics [4, 5]. According to studies, the exopolymer in biofilms inhibits the ability of leucocytes to pass through the biofilm, checking their capacity of leucocytes to degranulate, and stops them from producing reactive oxygen species (ROS), which prevents bacterial phagocytosis [6–8]. Previous investigations have stated that significant amounts of clinically important bacterial pathogens such as *Enterobacter cloacae, Escherichia coli, Klebsiella pneumonia*, *Pseudomonas aeruginosa, Staphylococcus aureus, S. epidermidis,* etc. possess the ability to develop biofilms [4, 9–11]. In addition, biofilms are also known to spread diseases through colonizing surgical instruments, which include central venous catheters, urinary catheters, joint prostheses, pacemakers, etc. [11, 12]. Furthermore, biofilm has been associated with chronic wounds, lung infections in cystic fibrosis patients, and dental caries [13].

In this chapter, we will describe the clinically important bacterial pathogens of the mouth, gut, lungs, and skin. Moreover, the formation and regulation of bacterial biofilm as well as pathogenicity, its mechanisms, and the eradication of biofilm by nanoparticles will also be discussed. This information echoes advancements in microbiome diagnostics and shows how biofilm is formed and regulated. A closer examination of biofilm provides more clarity on the inherent strengths and weaknesses of biofilm. It highlights the need to realize that biofilm is not simply a more significant number of wound pathogens but a sophisticated biological process that requires specific, targeted care. This study also highlights how different types of nanoparticles help in the eradication of bacterial biofilm and shows that nanoparticles have an excellent capacity for the eradication of bacterial biofilm and that different types of nanoparticles act in different ways in order to eradicate biofilm.
